Toxoplasma gondii (T. gondii) is an apicomplexan protozoan of world-wide medical importance. Humans are infected by T. gondii through contact with feces from infected cats, by the consumption of undercooked meat from infected animals, or by transmission from infected mother to fetus. This parasite can cause systemic infection and widespread organ damage in immunocompromised individuals and neonates. Infection of immunocompetent adults can result in fever and adenopathy (15). Serological studies indicate that T. gondii could be associated with chronic neuropsychiatric diseases or behavioral abnormalities in some populations (1, 17).
Available medications for the prevention and treatment of toxoplasma infection show limited efficacy and have substantial side effects (6). Published studies have indicated that the naturally occurring 1,2,4-trioxane artemisinin and artemisinin derivatives such as artemether, originally developed for the treatment of malaria, have the ability to inhibit toxoplasma replication in vitro (2, 4, 7, 13). While these trioxanes have a number of advantages in terms of rapid action and low levels of toxicity, they are limited in terms of absorption, bioavailability, and short half-life (i.e., easy hydrolysis into toxic dihydroartemisinin) (11, 12). Thus, what is needed are improved derivatives of artemisinin having not only rapid action and low levels of toxicity, but also better absorption, bioavailability, and longer half-lives for inhibiting the replication of T. gondii. 